The normal function of the cerebral cortex depends upon a complex neuronal circuitry. For example, pyramidal cells, which are the predominant excitatory neurons in the cortex, have axonal and dendritic arbors which are specific for select cortical layers. It is unknown what molecular signals control this specificity of intracortical connections. Recent data suggest ephrins, a family of membrane attached proteins, as attractive candidate molecules in the regulation of intracortical circuitry. The goal of this proposal to examine the role of ephrins in the development of intracortical connections within the visual cortex. First, the expression of ephrin ligands and their Eph receptors will be examined in the developing visual cortex. Second, the effects of genetically and biochemically manipulating the interactions between ephrin ligands and their receptors will be examined. These data will provide insight into the role of ephrins in regulating intracortical connections. A clearer understanding of cortical pyramidal cell development is clinically imperative as developmental disorders, such as Down's syndrome and Rett syndrome, have been shown to result in alterations in pyramidal cell morphology. In addition, information from these studies may help to elucidate the mechanisms responsible for morphological and functional alterations in pyramidal cell dendrites and axons due to aging and cortical injury.